PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Bohnert, B.N. ; Daiminger, S.* ; Wörn, M.* ; Sure, F.* ; Staudner, T.* ; Ilyaskin, A.V.* ; Batbouta, F.* ; Janessa, A.* ; Schneider, J.C.* ; Essigke, D.* ; Kanse, S.* ; Haerteis, S.* ; Korbmacher, C.* ; Artunc, F.

Urokinase-type plasminogen activator (uPA) is not essential for epithelial sodium channel (ENaC)-mediated sodium retention in experimental nephrotic syndrome.

Acta Physiol. 227:e13286 (2019)
Postprint Research data DOI PMC
Open Access Green
Aim In nephrotic syndrome, aberrantly filtered plasminogen (plg) is converted to active plasmin by tubular urokinase-type plasminogen activator (uPA) and thought to lead to sodium retention by proteolytic activation of the epithelial sodium channel (ENaC). This concept predicts that uPA is an important factor for sodium retention and that inhibition of uPA might be protective in nephrotic syndrome. Methods Activation of amiloride-sensitive currents by uPA and plg were studied in Xenopus laevis oocytes expressing murine ENaC. In doxorubicin-induced nephrotic mice, uPA was inhibited pharmacologically by amiloride and genetically by the use of uPA-deficient mice (uPA(-/-)). Results Experiments in Xenopus laevis oocytes expressing murine ENaC confirmed proteolytic ENaC activation by a combination of plg and uPA which stimulated amiloride-sensitive currents with concomitant cleavage of the ENaC gamma-subunit at the cell surface. Treatment of nephrotic wild-type mice with amiloride inhibited urinary uPA activity, prevented urinary plasmin formation and sodium retention. In nephrotic mice lacking uPA (uPA(-/-)), urinary plasmin formation from plg was suppressed and urinary uPA activity absent. However, in nephrotic uPA(-/-) mice, sodium retention was not reduced compared to nephrotic uPA(+/+) mice. Amiloride prevented sodium retention in nephrotic uPA(-/-) mice which confirmed the critical role of ENaC in sodium retention. Conclusion uPA is responsible for the conversion of aberrantly filtered plasminogen to plasmin in the tubular lumen in vivo. However, uPA-dependent plasmin generation is not essential for ENaC-mediated sodium retention in experimental nephrotic syndrome.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
5.868
1.264
16
24
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Amiloride ; Epithelial Sodium Channel (enac) ; Nephrotic Syndrome ; Plasminogen ; Sodium Retention ; Urokinase-type Plasminogen Activator; Gamma-subunit; Proteolytic Activation; Collecting Duct; Enac; Cleavage; Aldosterone; Maturation; Sites
Language english
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 1748-1708
e-ISSN 1748-1716
Journal Acta Physiologica
Quellenangaben Volume: 227, Issue: 4, Pages: , Article Number: e13286 Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502400-001
DOI 10.1111/apha.13286
WOS ID WOS:000496158200006
Scopus ID 85066145038
PubMed ID 31006168
Erfassungsdatum 2019-05-09
[➜Report correction]